Bioequivalence and Bioavailability Forum • Another vicious circle

Another vicious circle [Software]

posted by Helmut – Vienna, Austria, 2013-01-06 03:21 (4505 d 04:19 ago) – Posting: # 9791
Views: 12,726

Dear Detlew!

❝ ❝ ... In the meantime I finished my balanced cross-over sim’s. n 12–60, CV 6–100%. With my grid I have 306·10⁶ sim’s each. With rounding I got 24 (7.84%) empiric alphas significantly >0.05; without 11 (3.59%).

❝

❝ How do you interpret the un-rounded results?

Had to have a break. Let’s see what I got from n 12, CV 6%, 10⁶ sim’s:
50331 studies passed when BE was defined as the unrounded upper CL ≤1.25 (α_emp n.s.). 50503 studies passed based on round(CLhi,4) ≤1.25 (α_emp sign. >0.05). In increasing order (skipping 170):

    Unrounded.lo     Unrounded.hi  Rd.lo  Rd.hi

1.14406215516423 1.25000008857710 1.1441 1.2500

…

1.16009942086582 1.25004974319996 1.1601 1.2500

and

    Unrounded.lo         Unrounded.hi         Rounded.lo         Rounded.hi

Min.   :1.11998223   Min.   :1.25000009   Min.   :1.12000000   Min.   :1.25

1st Qu.:1.14730961   1st Qu.:1.25001184   1st Qu.:1.14730000   1st Qu.:1.25

Median :1.16346327   Median :1.25002528   Median :1.16345000   Median :1.25

Mean   :1.16222013   Mean   :1.25002554   Mean   :1.16221977   Mean   :1.25

3rd Qu.:1.17608605   3rd Qu.:1.25003838   3rd Qu.:1.17610000   3rd Qu.:1.25

Max.   :1.20299871   Max.   :1.25004974   Max.   :1.20300000   Max.   :1.25

Verdict: Duno. Wasn’t there a guy having a heading “Science vs. Regulations” in one of his slides? I would say the AR is based on the maximum acceptable ∆ and BE means 1–∆ ≤ CI ≤ (1–∆)^-1. No fucking rounding here.
It’s ^so_o_oo convenient^* that 100%/0.8 gives an integer. Stupidity starts with rounding the periodic decimal 100%/0.9=111.11% to 111.11% precisely (for Canada’s lumberjacks to 112.00%).
There is no rounding in theoretical statistics at all. So I have mixed feelings.

If I don’t round I’m closer to theory and it is less likely to get significant results.
Mr X will tell me “Nice simulations but not based on our BE criterion.”
If I round I get more significant results.
Mr X will tell me “Nice simulations proving the patient’s risk is not maintained.”

Convenience [sic] was the winning argument when regulations changed from an additive (AR 80–120%) to a multiplicative model (AR 80-125%). Really. See also this slide.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

Rounding Helmut 2013-01-01 16:51 [Software]
- Rounding d_labes 2013-01-02 12:51
  - Rounding Helmut 2013-01-04 17:35
    - Rounding d_labes 2013-01-05 19:25
      - Rounding Helmut 2013-01-05 20:13
        
        Sim’s are sim’s are sim’s d_labes 2013-01-05 20:57
      - Another vicious circleHelmut 2013-01-06 02:21
        
        Where all these numbers came from? d_labes 2013-01-07 15:52
        
        Flaw in the GL? Helmut 2013-01-07 17:29
        
        Flaw in the GL? d_labes 2013-01-08 11:44
        
        What a mess! Helmut 2013-01-08 19:08
        
        What a mess! d_labes 2013-01-09 10:33
        
        What a mess! Helmut 2013-01-09 15:18
- Rounding ElMaestro 2013-01-02 16:12
  - Abandon rounding Helmut 2013-01-02 17:04
- Rounding yjlee168 2013-01-05 23:15
  - Rounding Helmut 2013-01-06 03:29
  - Rounding Helmut 2013-01-06 15:34
    - Rounding yjlee168 2013-01-06 23:38